ArticleProceedings of the National Academy of Sciences of the United States of America2017
Nrf2 mitigates LRRK2- and α-synuclein-induced neurodegeneration by modulating proteostasis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers.
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Who cites it
76 citing papers in PubMed, 119 citations in OpenAlex.
- Predictive Cellular Signatures from Live Human Motor Neurons Distinguish TDP-43 ALS and Enable ALS Subtype Stratification.bioRxiv : the preprint server for biology · 2026Article
- Role of NRF2 in Electroacupuncture's Effects on Postoperative Cognitive Impairment in Rats.Neuropsychiatric disease and treatment · 2026Article
- Review
- Micro- and Nanoplastics and Functional Nutrients in Human Health: Epigenetic Mechanisms and Cellular Resilience Signaling in Brain Insulin Resistance and the Risk of Alzheimer's Disease.International journal of molecular sciences · 2025Review
- Nrf2 signaling in bone health: unlocking new avenues for osteoporosis management.Inflammopharmacology · 2025Review
- The Multifaceted Role of LRRK2 in Parkinson's Disease.Brain sciences · 2025Review
- A2-Astrocyte Activation by Short-Term Hypoxia Rescues α-Synuclein Pre-Formed-Fibril-Induced Neuronal Cell Death.Biomedicines · 2025Article
- Proteostasis Decline and Redox Imbalance in Age-Related Diseases: The Therapeutic Potential of NRF2.Biomolecules · 2025Review
- Mild Chronic Colitis Exacerbates Intracerebral Inflammation in Mice with Parkinson's Disease Through LRRK2-Mediated Regulation of NF-κB Activation and Inhibition of Nrf2.Journal of inflammation research · 2025Article
- Reactive oxygen species control protein degradation at the mitochondrial import gate.Molecular cell · 2024Article
- NRF2 in age-related musculoskeletal diseases: Role and treatment prospects.Genes & diseases · 2024Review
- Unraveling neuroprotection in Parkinson's disease: Nrf2-Keap1 pathway's vital role amidst pathogenic pathways.Inflammopharmacology · 2024Review
- Hypoxia Pathways in Parkinson's Disease: From Pathogenesis to Therapeutic Targets.International journal of molecular sciences · 2024Review
- Role of Astrogliosis in the Pathogenesis of Parkinson's Disease: Insights into Astrocytic Nrf2 Pathway as a Potential Therapeutic Target.CNS & neurological disorders drug targets · 2024Review
- Alpha-Synuclein Contribution to Neuronal and Glial Damage in Parkinson's Disease.International journal of molecular sciences · 2023Review
- A Triterpenoid Lupeol as an Antioxidant and Anti-Neuroinflammatory Agent: Impacts on Oxidative Stress in Alzheimer's Disease.Nutrients · 2023Review
- Targeting Nrf2 signaling pathway and oxidative stress by resveratrol for Parkinson's disease: an overview and update on new developments.Molecular biology reports · 2023Review
- Early-Life Exposure to Commercial Formulation Containing Deltamethrin and Cypermethrin Insecticides Impacts Redox System and Induces Unexpected Regional Effects in Rat Offspring Brain.Antioxidants (Basel, Switzerland) · 2023Article
- Genetic modifiers of synucleinopathies-lessons from experimental models.Oxford open neuroscience · 2023Review
- Apomorphine Reduces A53T α-Synuclein-Induced Microglial Reactivity Through Activation of NRF2 Signalling Pathway.Cellular and molecular neurobiology · 2022Article
16 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Mutations in leucine-rich repeat kinase 2 (LRRK2) and α-synuclein lead to Parkinson's disease (PD). Disruption of protein homeostasis is an emerging theme in PD pathogenesis, making mechanisms to reduce the accumulation of misfolded proteins an attractive therapeutic strategy. We determined if activating nuclear factor erythroid 2-related factor (Nrf2), a potential therapeutic target for neurodegeneration, could reduce PD-associated neuron toxicity by modulating the protein homeostasis network. Using a longitudinal imaging platform, we visualized the metabolism and location of mutant LRRK2 and α-synuclein in living neurons at the single-cell level. Nrf2 reduced PD-associated protein toxicity by a cell-autonomous mechanism that was time-dependent. Furthermore, Nrf2 activated distinct mechanisms to handle different misfolded proteins. Nrf2 decreased steady-state levels of α-synuclein in part by increasing α-synuclein degradation. In contrast, Nrf2 sequestered misfolded diffuse LRRK2 into more insoluble and homogeneous inclusion bodies. By identifying the stress response strategies activated by Nrf2, we also highlight endogenous coping responses that might be therapeutically bolstered to treat PD.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.